G protein coupled receptor 18 activation during experimental colitis in mice

Ulcerative colitis (UC) belongs to inflammatory bowel disease (IBD), a group of chronic disorders of the gastrointestinal (GI) tract with unknown etiopathogenesis. The prevalence of IBD is increasing, and available therapeutic options do not lead to complete remission; therefore, there is a need to identify novel pharmaceutical strategies for UC. The aim of our study was to evaluate the suitability of the PSB-KK-1415, the G protein coupled receptor 18 (GPR18) receptor agonist, in the treatment of intestinal inflammation in mice. The impact of PSB-KK-1415 on the viability of human epithelial cell line CCD 841 CON was assessed using MTT assay. Dextran sodium sulfate (DSS) was used to induce colitis in mice. Colonic samples were collected at different stages of disease and Gpr18 expression was determined using real time RT-PCR. In the DSS model, the mice were treated with PSB-KK-1415 (5 mg/kg once daily) by different routes of administration. The anti-inflammatory potential of PSB-KK-1415 in vivo was evaluated based on macroscopic and microscopic scoring systems. As a result PSB-KK-1415 did not affect the viability of CCD 841 CON cells after 24 and 48 hours. The mRNA expression of GPR18 was significantly increased in the early and moderate stages of colitis as compared to the control group and decreased in severe colitis and during recovery. In the acute mouse model of UC, 5 mg/kg PSB-KK-1415 injected intraperitoneally tended to reduce the area of inflammation and improved the intestinal wall thickness as compared to mice with colitis. PSB-KK-1415 decreased MPO activity. No significant differences in anti-inflammatory effect were found with regard to the route of administration. In the chronic model of DSS-induced colitis, PSB-KK-1415 demonstrated anti-inflammatory properties, evidenced by a decreased area of inflammation in the colon and improved intestinal thickness as compared to inflamed animals. Our findings indicate that activation of the GPR18 receptor may be a potential target for modulation the course of chronic colitis in mice.